PYGO1_HUMAN
ID PYGO1_HUMAN Reviewed; 419 AA.
AC Q9Y3Y4; A7Y2D6;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Pygopus homolog 1;
GN Name=PYGO1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11955446; DOI=10.1016/s0092-8674(02)00679-7;
RA Kramps T., Peter O., Brunner E., Nellen D., Froesch B., Chatterjee S.,
RA Murone M., Zuellig S., Basler K.;
RT "Wnt/wingless signaling requires BCL9/legless-mediated recruitment of
RT pygopus to the nuclear beta-catenin-TCF complex.";
RL Cell 109:47-60(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Heart;
RA Wang C.D., Wu X.S., Liu M.Y.;
RT "Research on human heart developmental candidate gene PYGO1.";
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 303-419 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH BCL9L; CDC73 AND CTNNB1.
RX PubMed=17113272; DOI=10.1016/j.mod.2006.09.006;
RA Hoffmans R., Basler K.;
RT "BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires
RT Pygopus for its function in Wg/Wnt signaling.";
RL Mech. Dev. 124:59-67(2007).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 333-397 IN COMPLEX WITH ZINC
RP IONS; HISTONE H3K4ME2 AND BCL9, INTERACTION WITH BCL9 AND HISTONE H3KME1;
RP H3K4M2; H3K4ME3, ZINC-BINDING, AND MUTAGENESIS OF GLU-349; VAL-350;
RP ASN-351; GLN-354; ALA-356; ILE-357; GLU-360 AND TRP-366.
RX PubMed=18498752; DOI=10.1016/j.molcel.2008.03.011;
RA Fiedler M., Sanchez-Barrena M.J., Nekrasov M., Mieszczanek J., Rybin V.,
RA Muller J., Evans P., Bienz M.;
RT "Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling
RT complex.";
RL Mol. Cell 30:507-518(2008).
CC -!- FUNCTION: Involved in signal transduction through the Wnt pathway.
CC -!- SUBUNIT: Interacts with BCL9 via The PHD-type zinc finger motiv, and
CC thereby becomes part of the nuclear beta-catenin/TCF complex.
CC Identified in a complex with BCL9L, CDC73, CTNNB1 and PYGO1. Interacts
CC with histone H3 mono-, di- or tri-methylated at 'Lys4' (H3K4me1,
CC H3K4me2, H3K4me3); the interaction is enhanced by the interaction with
CC BCL9. {ECO:0000269|PubMed:17113272, ECO:0000269|PubMed:18498752}.
CC -!- INTERACTION:
CC Q9Y3Y4; P61769: B2M; NbExp=3; IntAct=EBI-3397474, EBI-714718;
CC Q9Y3Y4; O00512: BCL9; NbExp=8; IntAct=EBI-3397474, EBI-533127;
CC Q9Y3Y4; P27797: CALR; NbExp=3; IntAct=EBI-3397474, EBI-1049597;
CC Q9Y3Y4; P36957: DLST; NbExp=3; IntAct=EBI-3397474, EBI-351007;
CC Q9Y3Y4; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-3397474, EBI-1055945;
CC Q9Y3Y4; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-3397474, EBI-11952721;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y3Y4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3Y4-2; Sequence=VSP_056648;
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DR EMBL; AF457207; AAL91370.1; -; mRNA.
DR EMBL; EF625686; ABU93489.1; -; mRNA.
DR EMBL; AC012378; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022083; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049925; CAB43209.1; -; mRNA.
DR CCDS; CCDS10155.1; -. [Q9Y3Y4-1]
DR CCDS; CCDS81885.1; -. [Q9Y3Y4-2]
DR PIR; T08663; T08663.
DR RefSeq; NP_001317255.1; NM_001330326.1. [Q9Y3Y4-2]
DR RefSeq; NP_056432.1; NM_015617.2. [Q9Y3Y4-1]
DR RefSeq; XP_011519748.1; XM_011521446.2.
DR PDB; 2VP7; X-ray; 1.65 A; A=333-402.
DR PDB; 2VPB; X-ray; 1.59 A; A=333-397.
DR PDB; 2VPD; X-ray; 2.77 A; A/C=333-398.
DR PDB; 2VPE; X-ray; 1.70 A; A/C=340-398.
DR PDB; 2VPG; X-ray; 1.60 A; A/C=340-398.
DR PDBsum; 2VP7; -.
DR PDBsum; 2VPB; -.
DR PDBsum; 2VPD; -.
DR PDBsum; 2VPE; -.
DR PDBsum; 2VPG; -.
DR AlphaFoldDB; Q9Y3Y4; -.
DR SMR; Q9Y3Y4; -.
DR BioGRID; 117557; 23.
DR IntAct; Q9Y3Y4; 27.
DR MINT; Q9Y3Y4; -.
DR STRING; 9606.ENSP00000302327; -.
DR iPTMnet; Q9Y3Y4; -.
DR PhosphoSitePlus; Q9Y3Y4; -.
DR BioMuta; PYGO1; -.
DR DMDM; 23396828; -.
DR jPOST; Q9Y3Y4; -.
DR MassIVE; Q9Y3Y4; -.
DR PaxDb; Q9Y3Y4; -.
DR PeptideAtlas; Q9Y3Y4; -.
DR PRIDE; Q9Y3Y4; -.
DR ProteomicsDB; 1817; -.
DR ProteomicsDB; 86087; -. [Q9Y3Y4-1]
DR Antibodypedia; 25101; 164 antibodies from 23 providers.
DR DNASU; 26108; -.
DR Ensembl; ENST00000302000.10; ENSP00000302327.6; ENSG00000171016.13. [Q9Y3Y4-1]
DR Ensembl; ENST00000563719.4; ENSP00000457777.1; ENSG00000171016.13. [Q9Y3Y4-2]
DR Ensembl; ENST00000645724.1; ENSP00000496139.1; ENSG00000171016.13. [Q9Y3Y4-2]
DR GeneID; 26108; -.
DR KEGG; hsa:26108; -.
DR MANE-Select; ENST00000563719.4; ENSP00000457777.1; NM_001367806.1; NP_001354735.1. [Q9Y3Y4-2]
DR UCSC; uc002adf.3; human. [Q9Y3Y4-1]
DR CTD; 26108; -.
DR GeneCards; PYGO1; -.
DR HGNC; HGNC:30256; PYGO1.
DR HPA; ENSG00000171016; Low tissue specificity.
DR MIM; 606902; gene.
DR neXtProt; NX_Q9Y3Y4; -.
DR OpenTargets; ENSG00000171016; -.
DR PharmGKB; PA134875127; -.
DR VEuPathDB; HostDB:ENSG00000171016; -.
DR eggNOG; ENOG502QTIZ; Eukaryota.
DR GeneTree; ENSGT00530000063948; -.
DR HOGENOM; CLU_686883_0_0_1; -.
DR InParanoid; Q9Y3Y4; -.
DR OMA; YNTFRMP; -.
DR OrthoDB; 919773at2759; -.
DR PhylomeDB; Q9Y3Y4; -.
DR TreeFam; TF333020; -.
DR PathwayCommons; Q9Y3Y4; -.
DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR SignaLink; Q9Y3Y4; -.
DR SIGNOR; Q9Y3Y4; -.
DR BioGRID-ORCS; 26108; 13 hits in 1074 CRISPR screens.
DR ChiTaRS; PYGO1; human.
DR EvolutionaryTrace; Q9Y3Y4; -.
DR GenomeRNAi; 26108; -.
DR Pharos; Q9Y3Y4; Tdark.
DR PRO; PR:Q9Y3Y4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9Y3Y4; protein.
DR Bgee; ENSG00000171016; Expressed in cortical plate and 118 other tissues.
DR Genevisible; Q9Y3Y4; HS.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; IDA:FlyBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0007289; P:spermatid nucleus differentiation; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00255; -.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00628; PHD; 1.
DR SMART; SM00249; PHD; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Metal-binding; Nucleus;
KW Reference proteome; Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..419
FT /note="Pygopus homolog 1"
FT /id="PRO_0000097121"
FT ZN_FING 340..398
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 1..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..388
FT /note="Interaction with H3K4me2"
FT REGION 373..391
FT /note="Interaction with BCL9"
FT /evidence="ECO:0000269|PubMed:18498752"
FT MOTIF 35..41
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 175..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 241..308
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..16
FT /note="MPAENSPAPAYKVSSH -> MSAEQEKDPISLKRVR (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_056648"
FT VARIANT 299
FT /note="P -> H (in dbSNP:rs11858624)"
FT /id="VAR_051292"
FT MUTAGEN 349
FT /note="E->A: Reduces interaction with H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 350
FT /note="V->E: Almost complete loss of interaction with
FT H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 351
FT /note="N->A: Reduces interaction with H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 354
FT /note="Q->A: Reduces interaction with H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 356
FT /note="A->E: Almost complete loss of interaction with
FT H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 357
FT /note="I->R: Loss of interaction with H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 360
FT /note="E->A: Loss of interaction with H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT MUTAGEN 366
FT /note="W->E: Loss of interaction with H3K4me2."
FT /evidence="ECO:0000269|PubMed:18498752"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:2VPG"
FT TURN 344..346
FT /evidence="ECO:0007829|PDB:2VPB"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:2VPB"
FT TURN 360..363
FT /evidence="ECO:0007829|PDB:2VPB"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:2VPB"
FT HELIX 369..372
FT /evidence="ECO:0007829|PDB:2VPB"
FT HELIX 376..384
FT /evidence="ECO:0007829|PDB:2VPB"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:2VPB"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:2VPB"
SQ SEQUENCE 419 AA; 45116 MW; D5D4E4AA416FD8E4 CRC64;
MPAENSPAPA YKVSSHGGDS GLDGLGGPGV QLGSPDKKKR KANTQGPSFP PLSEYAPPPN
PNSDHLVAAN PFDDNYNTIS YKPLPSSNPY LGPGYPGFGG YSTFRMPPHV PPRMSSPYCG
PYSLRNQPHP FPQNPLGMGF NRPHAFNFGP HDNSSFGNPS YNNALSQNVN MPNQHFRQNP
AENFSQIPPQ NASQVSNPDL ASNFVPGNNS NFTSPLESNH SFIPPPNTFG QAKAPPPKQD
FTQGATKNTN QNSSAHPPHL NMDDTVNQSN IELKNVNRNN AVNQENSRSS STEATNNNPA
NGTQNKPRQP RGAADACTTE KSNKSSLHPN RHGHSSSDPV YPCGICTNEV NDDQDAILCE
ASCQKWFHRI CTGMTETAYG LLTAEASAVW GCDTCMADKD VQLMRTRETF GPSAVGSDA
